New drug shows same antidepressant effect as ketamine, study shows

By Bill Hathaway

October 15, 2013

A drug under development seems to have similar antidepressant effects as previously observed with ketamine, but without the same level of dangerous side effects seen when the anesthetic is abused as a party drug, according to a new Yale-led study.

The findings of a randomized, placebo-controlled trial suggest a new generation of antidepressants that act upon the brain’s glutamate system may offer rapid relief for millions of people suffering from chronic depression who have not responded to existing antidepressant medications.

“This study suggests it is possible to selectively develop drugs that can capture the clinical benefits previously observed with ketamine without inducing the same level unwanted side effects,” said Gerard Sanacora, professor of psychiatry and lead author of the study published Oct. 15 in the journal Molecular Psychiatry.

Previous Yale studies have shown that ketamine can provide almost immediate relief to some patients suffering from chronic depression. Subsequent studies have begun to illustrate the molecular mechanisms that may explain its clinical benefits.

The current study includes Phase II data with lanicemine, one of several novel drugs under development that target the NMDA receptor for the neurotransmitter glutamate. For the past half century, antidepressant drugs have focused almost exclusively on the neurotransmitter systems for serotonin, norepinephrine, and dopamine.

The new study suggests the glutamatergic system is a viable target for antidepressant drug development that could lead to a truly new class of medications for people suffering from depression.

The study was funded by AstraZeneca Pharmaceuticals, which is developing the drug. Sanacora has received consulting fees and grant support from AstraZeneca, and is co-inventor of named on a patent application drug filed by Yale University for drugs with glutamate modulating activity.

This work was partially funded by the Yale Clinical and Translational Science Award (CTSA) grant from the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health.